[Efficacy and safety of ultra rapid lispro in the treatment of type 2 diabetes mellitus: a randomized controlled clinical trial].

Objective: To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus. Methods: This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A_1c (HbA_1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA_1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher's exact test. Results: Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA_1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA_1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient-year; P=0.040]. Conclusions: With good glycemic control, URLi showed non-inferiority for HbA_1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.